The present invention is directed to a biochemically active material, its production and an agent containing this active material.
Materials promoting growth, the so-called "growth stimulants", are typically employed in the feeding of animals for producing quicker growth and increased meat tissue production. The known growth promoting materials may be categorized as either antibiotics, synthetic chemical growth promoters or sexual hormones. The use of sexual hormones as growth promoters in the feeding of animals is forbidden by law in some countries, inter alia because of the sexual specificity, and as a result there have been several proposals for alternative materials. Thus, for example, plant extracts with possibly suitable properties, "phytoadaptogens", e.g. from Eleutherococcus senticosus, were recently tested; see Kaemerer et al, Der Praktische Tierarzt 9/1980, pages 748-760. However, limits are placed on the production of these types of growth promoters because of the very large amounts of plant starting material necessary to supply the quantities required. For example, if only 1% of this type of growth promoter is added to only 10% of the mixed poultry feed consumed in the Federal Republic of Germany, about 350,000 kg of Elutherococcus, on a dry weight basis, must be produced. Furthermore, the properties of such plant extracts vary in potency and desired result from crop to crop depending on the conditions of cultivation, harvesting, and type of plant growth; further considerable land areas are needed for cultivation.
A further group of plant materials coming into question, according to W. J. Mach, Die Ernaehrungsumschau 7 (1971) pp. 259-260, are the postmortal occurring, radical secondary products of reaction of the type of melanoidins, i.e. dark substances formed by the interaction of reducing sugars and amino acids when heated. This reaction is sometimes called the Maillard reaction. The knowledge of these materials leads inter alia to investigations over the chemism of postmortal compounds in brown hay which is said to cause an increased desire for food; see Handbuch der Futtermittel, Vol. 1, P. Parey, Berlin, (1967), but which has not yet been employed systematically.
The process of producing brown hay is indeed very difficult to control and no longer has any industrial significance. However, when the process is carried out as Emmerling was able to show more than 100 years ago, aromatic-quinoid secondary products result according to the principle of the reaction with nascent quinones, and these products too are considered to be melanoidins. Thus the term "melanoidin" stands for a collective concept of browned products as they occur, for example for the heating of many nutrients, either as desired or undesired reaction products; see Ernaehrungs-Umschau 1971, p. 295. As such they are poorly isolatable forms of postmortal plant secondary reaction products, sometimes called radical condensation products, which can have structural units having unpaired electrons that are detectable by ESR spectroscopy. Melanoidins furthermore can be found by intestinal bacteria under physiological conditions from plant ballast material, provided that it contains lignin; see Dirscherl, Revue Roumaine de Biochemie 1, (1966).
Natural materials which belong to the large and chemically ill-defined group of melanoidins are also found in relatively small amounts and different chemical properties in coffee extracts, bacterial cultures, e.g. B. subtilis, E. coli, among others, and in cultures of lower fungii such as actinomycelis. Furthermore melanoidins can be produced synthetically by chemical irradiation, e.g. UV+tyrosine. Such materials are also found in certain fermenting or rotting products such as in peat, beer and in many plant extracts. Most of these raw materials, however, are unsuited for industrial use, since they do not give industrial yields or are unsuited either chemically and/or physically.
Exhaustive work on the clarification of the human therapeutic effects on the digestive tract and the metabolism of melanoidins such as coffee melanoidins (Ernaehrungs Umschau, loc. cit.), so-called "carbo coffeae" and the "butter tea" of Tibet, however, show that the anti-hepatoxic activity of the group of materials of this type, the melanoidin acids, alone are not suited for growth promotion. The property of brown or burning hay to increase the desire for food is probably more a matter of physiological effect due to the aroma than a true growth promotion effect.
According to Schole in a publication based on a lecture held in Cuxhaven on Oct. 21, 1981 in the Federal Republic of Germany, the growth promoting activity of anabolic materials depends primarily on the ability of a material to stimulate the synthesis metabolism of cells, liberated by the reduction of the activity of radical forming enzymes in the membrane system of the cells. These radical forming enzymes, by oxidation of the sensitive SH-enzyme contained in all cytoplasmatic and nuclear synthesis cycles, limit the synthesis metabolism. The cell redox systems, e.g. the glutathione system, must provide for the protection of the SH-enzyme. However, if the radical forming membrane enzyme is blocked by factors supplied from outside the system then the synthesis metabolism of the cells is increased through activation of the synthesis cycles in the cytoplasm and cell nucleus. As anobilic factors there are considered materials which, in turn, represent active redox, electron donor-acceptor systems. The increased synthesis metabolism in turn requires an increased amount of energy in the form of adenosine triphosphate (ATP). To guarantee this energy a hormonal counter reaction is liberated in the organism in the presence of an intensified synthesis metabolism. The catabolically acting hormone of the adrenal cortex as well as thyroxine provide for the breakdown of reserve material and therewith for the manufacture of ATP. The cells thus then are capable of optimal output if an anobilic factor reduces the enzyme radical retarding the synthesis metabolism and simultaneously provides for catabolic factors, namely for sufficient ATP, provided no exceeding catabolic hormone or other reaction occurs.
It has now been found that experimentally comprehensible metabolism regulation effects (adaptogen activity) of plant growth promoters depend on the coexistence of both catabolically and anabolically active structural elements. Experiments show that the fine tuning of anabolic and catabolic activities of a plant growth promoter suited for the rearing of animals is an unconditional prerequisite.
Based on these experiments a renewed investigation of water-soluble melanoidins was undertaken, that is the alkali salt of the melanoidin acid after cation exchange that form a truly water soluble material in the pH range of 7.0 to 5.0. Surprisingly the anabolic and catabolic activity of lignoid melanoidins having anabolically and catabolically active structural units, comprising aromatic quinoid, resorbable secondary products of radical condensation reactions, can be selectively controlled to be equalized, while the catabolic activity is definitely inhibited. Without this controlled equalization of the anabolic and catabolic activities a permanent growth increase in the rearing of animals through the use of lignoid melanoidins as growth promoters is not obtained. It has further been found that the carbonized products of natural lignoid materials suited for use in the invention contain structural units of the quinone, semiquinone and quinhydrone type, and have unpaired electrons detectable through ESR spectroscopy.